Activation, Pharmacokinetics, and Mechanism of Action of BCI-101: BCI-101 is a pro-drug for the active forms of vitamin D2. This drug is less toxic, as evidenced by less nephracalcinosis, hypercalcemia and hypercalciuria, than its vitamin D3 counterpart. The mechanism for this lower toxicity may be attributed to three major factors: 1) as a pro-drug, the compound is inactive on intestinal calcium transport when it is absorbed after oral administration; 2) the metabolism in the liver to active compounds differs from its vitamin D3 counterpart; and 3) the compound may form active metabolites in the target tissues. Radiolabelled BCI-101 will be used as a tool to assess the third hypothesis. Animals will be orally administered this compound in a suitable vehicle. At specified times after dosing blood samples will be drawn and the amount and identification of the radioactive compound(s) will be determined. At study termination, the animal will be euthanized and tissues removed. Activation and Pharmacokinetics of LR-110: Vitamin D2 has been shown to be metabolized in animals and human beings to LR-110 as well as 25-hydroxyvitamin D2. LR-110 can be metabolized into an active compound, LR-103. In animal studies, LR-103 produces less hypercalcemia and hypercalciuria than the active metabolite of vitamin D3. Radiolabelled LR-110 will be used to determine whether this compound can be used as a pro-drug for LR-103. Because the metabolite of LR-110 is active at very low levels, i.e. 10-50 x 10-12 grams/mL, a radiolabelled LR-110 of high specific activity is required to study the activation of this compound. ADME studies will be performed with this compound on animals. Animals will be orally administered this compound in a suitable vehicle. At specified times after dosing blood samples will be withdrawn and the amount and identification of the radioactive compound(s) will be determined. Urine and feces will be collected and the radioactivity quantified in the excreta. These data provide mass balance data of the compound. At study termination, the animal will be euthanized and tissues removed. Binding of the radiolabelled compound to blood will also be assessed. Pharmacokinetics and Mechanism of Action of LR-103: LR-103 is an active metabolite of vitamin D2. After therapeutic doses of vitamin D2 to vitamin D-deficient patients, LR-103 and 1_,25-dihydroxyvitamin D2, another active metabolite of this vitamin, are detected in blood. In animal studies LR-103 produces less hypercalcemia and hypercalciuria than the active metabolite of vitamin D3. As an active vitamin D with less side effects, LR-103 is a potential therapy for hyperproliferative diseases such as a variety of cancers and psoriasis. Because LR-103 is active at very low levels, i.e. 10-50 x 10-12 grams/mL, a radiolabelled LR-103 of high specific activity is required to track this compound in intact animals. ADME studies will be performed with this compounds in animals, and if shown of therapeutic use in the clinic, in human beings. Animals will be orally administered this compound in a suitable vehicle. At specified times after dosing blood samples will be withdrawn and the amount and identification of the radioactive compound(s) will be determined. Urine and feces will be collected and the radioactivity quantified in the excreta. These data provide mass balance data of the compound. At study termination, the animal will be euthanized and tissues removed. User Details: Experiment Details: User Number: 1706 Tritiation City, State: Madison, WI HPLC Funding Source: Industry NMR Charge: $6349.27 5 days Program Income: $6348.20 5 compounds Secondary Users: Dr. Glenville Jones, Queen's University, B00of Biochemistry, Canada Dr. Alex Brown, Washington University, St. Louis, MO